title: The progressive ankylosis protein regulates cementum apposition and extracellular matrix composition.
abstract: OBJECTIVE
  Tooth root cementum is sensitive to modulation of inorganic pyrophosphate (PP(i)), an inhibitor of hydroxyapatite precipitation. Factors increasing PP(i) include progressive ankylosis protein (ANK) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) while tissue nonspecific alkaline phosphatase hydrolyzes PP(i). Studies here aimed to define the role of ANK in root and cementum by analyzing tooth development in Ank knock-out (KO) mice versus wild type.
  
  
  METHODS
  Periodontal development in KO versus control mice was analyzed by histology, histomorphometry, immunohistochemistry, in situ hybridization, electron microscopy, and nanoindentation. Cementoblast cultures were used in vitro to provide mechanistic underpinnings for PP(i) modulation of cell function.
  
  
  RESULTS
  Over the course of root development, Ank KO cervical cementum became 8- to 12-fold thicker than control cervical cementum. Periodontal ligament width was maintained and other dentoalveolar tissues, including apical cementum, were unaltered. Cervical cementum uncharacteristically included numerous cells, from rapid cementogenesis. Ank KO increased osteopontin and dentin matrix protein 1 gene and protein expression, and markedly increased NPP1 protein expression in cementoblasts but not in other cell types. Conditional ablation of Ank in joints and periodontia confirmed a local role for ANK in cementogenesis. In vitro studies employing cementoblasts indicated that Ank and Enpp1 mRNA levels increased in step with mineral nodule formation, supporting a role for these factors in regulation of cementum matrix mineralization.
  
  
  CONCLUSIONS
  ANK, by modulating local PP(i), controls cervical cementum apposition and extracellular matrix. Loss of ANK created a local environment conducive to rapid cementogenesis; therefore, approaches modulating PP(i) in periodontal tissues have potential to promote cementum regeneration.
authors.affiliation: Department of Periodontics, University of Washington School of Dentistry, Seattle, Wash. 98195, USA. blfoster@u.washington.edu
authors.forename: B L
authors.initials: BL
authors.lastname: Foster
authors.forename: K J
authors.initials: KJ
authors.lastname: Nagatomo
authors.forename: S O
authors.initials: SO
authors.lastname: Bamashmous
authors.forename: K A
authors.initials: KA
authors.lastname: Tompkins
authors.forename: H
authors.initials: H
authors.lastname: Fong
authors.forename: D
authors.initials: D
authors.lastname: Dunn
authors.forename: E Y
authors.initials: EY
authors.lastname: Chu
authors.forename: C
authors.initials: C
authors.lastname: Guenther
authors.forename: D M
authors.initials: DM
authors.lastname: Kingsley
authors.forename: R B
authors.initials: RB
authors.lastname: Rutherford
authors.forename: M J
authors.initials: MJ
authors.lastname: Somerman
mesh_terms: D000818:Animals; D003739:Dental Cementum / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D028061:Phosphate Transport Proteins / Q000235:genetics / Q000378:metabolism*; D014070:Tooth / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D014092:Tooth Root / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D028061:Phosphate Transport Proteins; C410982:ank protein, mouse